By the time diseases of the retina are detected, serious damage has often already been done. An advanced optical imaging instrument called the adaptive optics scanning laser ophthalmoscopy (AOSLO) can be used to directly visualize the cellular structure of the retina in the living human eye. Adaptive optics is a technology for measuring and correcting the optical imperfections in the human eye. When adaptive optics is combined with an imaging platform, highly detailed images of the human retina can be acquired. Our research utilizes this technology to image cells in patients eyes through the newly-established Adaptive Optics Clinic within the NIH Clinical Center. Currently the interpretation of adaptive optics images is challenging in patients with diseases since in most cases highly detailed images of clinical lesions have never been imaged before. Therefore we are continuing a multi-year effort to assemble a database of images of eyes from healthy volunteers. Characterization of this data will aid in the interpretation of patient data and will be useful for statistical comparisons. In particular, we have developed sophisticated, novel image analysis and processing algorithms for the computer aided analysis of adaptive optics imaging data which will greatly enhance and accelerate our progress towards completing this normal database, noting that the processing of adaptive optics data is highly time consuming and labor intensive. These algorithms may lead to new imaging biomarkers and metrics for the quantitative valuation of disease. We are particularly interested in exploring new technologies for improving our state-of-the-art, custom-built adaptive optics instrument in the NEI eye clinic with the overarching goal of augmenting the translational research capabilities at the NIH Clinical Center. Through collaboration with Dr. Dubra at the Medical College of Wisconsin and Dr. Fariss of the NEI, we have invented a new method to simultaneously image the retinal pigment epithelial cells alongside the photoreceptors directly inside the living human eye. In addition, we are collaborating with Dr. Yang of the University of Rochester and Drs. Pursley and Pohida, CIT, to explore avenues for improving the eye tracking capabilities for adaptive optics retinal imaging and Dr. Hammer of the FDA to explore complementary advanced imaging modalities compatible with adaptive optics. Progress towards these projects are facilitated by ongoing collaborations with Howard Metger and with the NIH Library for custom machining or 3D printing of components related to various modules within the custom-built adaptive optics instrument. Finally, through collaboration with Dr. Cukras, NEI, and other clinicians, we are refining methods for longitudinal tracking of single cells in the living human eye, in patients with various retinal degenerations. Monitoring the progression of disease in an actual patient at the cell-to-cell level may provide new insights into the mechanisms of retinal diseases that cause blindness.